2c1m: Difference between revisions

← Older edit

Proteopedia Page Contributors and Editors (what is this?)Proteopedia Page Contributors and Editors (what is this?)

OCA

@@ Line 1: / Line 1: @@
-{{STRUCTURE_2c1m|  PDB=2c1m  |  SCENE=  }}
-===NUP50:IMPORTIN-ALPHA COMPLEX===
-{{ABSTRACT_PUBMED_16222336}}
-==Disease==
+==Nup50:importin-alpha complex==
-[[http://www.uniprot.org/uniprot/NUP50_MOUSE NUP50_MOUSE]] Note=Defects in Nup50 are the cause of neural tube defects, exencephaly and intrauterine growth retardation.
+<StructureSection load='2c1m' size='340' side='right'caption='[[2c1m]], [[Resolution|resolution]] 2.20&Aring;' scene=''>
+== Structural highlights ==
+<table><tr><td colspan='2'>[[2c1m]] is a 2 chain structure with sequence from [https://en.wikipedia.org/wiki/Mus_musculus Mus musculus]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=2C1M OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=2C1M FirstGlance]. <br>
+</td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 2.2&#8491;</td></tr>
+<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[https://proteopedia.org/fgij/fg.htm?mol=2c1m FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2c1m OCA], [https://pdbe.org/2c1m PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=2c1m RCSB], [https://www.ebi.ac.uk/pdbsum/2c1m PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=2c1m ProSAT]</span></td></tr>
+</table>
+== Function ==
+[https://www.uniprot.org/uniprot/IMA1_MOUSE IMA1_MOUSE] Functions in nuclear protein import as an adapter protein for nuclear receptor KPNB1. Binds specifically and directly to substrates containing either a simple or bipartite NLS motif. Docking of the importin/substrate complex to the nuclear pore complex (NPC) is mediated by KPNB1 through binding to nucleoporin FxFG repeats and the complex is subsequently translocated through the pore by an energy requiring, Ran-dependent mechanism. At the nucleoplasmic side of the NPC, Ran binds to importin-beta and the three components separate and importin-alpha and -beta are re-exported from the nucleus to the cytoplasm where GTP hydrolysis releases Ran from importin. The directionality of nuclear import is thought to be conferred by an asymmetric distribution of the GTP- and GDP-bound forms of Ran between the cytoplasm and nucleus.
+== Evolutionary Conservation ==
+[[Image:Consurf_key_small.gif|200px|right]]
+Check<jmol>
+  <jmolCheckbox>
+    <scriptWhenChecked>; select protein; define ~consurf_to_do selected; consurf_initial_scene = true; script "/wiki/ConSurf/c1/2c1m_consurf.spt"</scriptWhenChecked>
+    <scriptWhenUnchecked>script /wiki/extensions/Proteopedia/spt/initialview01.spt</scriptWhenUnchecked>
+    <text>to colour the structure by Evolutionary Conservation</text>
+  </jmolCheckbox>
+</jmol>, as determined by [http://consurfdb.tau.ac.il/ ConSurfDB]. You may read the [[Conservation%2C_Evolutionary|explanation]] of the method and the full data available from [http://bental.tau.ac.il/new_ConSurfDB/main_output.php?pdb_ID=2c1m ConSurf].
+<div style="clear:both"></div>
+<div style="background-color:#fffaf0;">
+== Publication Abstract from PubMed ==
+Nuclear import of proteins containing classical nuclear localization signals (NLS) is mediated by the importin-alpha:beta complex that binds cargo in the cytoplasm and facilitates its passage through nuclear pores, after which nuclear RanGTP dissociates the import complex and the importins are recycled. In vertebrates, import is stimulated by nucleoporin Nup50, which has been proposed to accompany the import complex through nuclear pores. However, we show here that the Nup50 N-terminal domain actively displaces NLSs from importin-alpha, which would be more consistent with Nup50 functioning to coordinate import complex disassembly and importin recycling. The crystal structure of the importin-alpha:Nup50 complex shows that Nup50 binds at two sites on importin-alpha. One site overlaps the secondary NLS-binding site, whereas the second extends along the importin-alpha C-terminus. Mutagenesis indicates that interaction at both sites is required for Nup50 to displace NLSs. The Cse1p:Kap60p:RanGTP complex structure suggests how Nup50 is then displaced on formation of the importin-alpha export complex. These results provide a rationale for understanding the series of interactions that orchestrate the terminal steps of nuclear protein import.
-==Function==
+Nup50/Npap60 function in nuclear protein import complex disassembly and importin recycling.,Matsuura Y, Stewart M EMBO J. 2005 Nov 2;24(21):3681-9. Epub 2005 Oct 13. PMID:16222336<ref>PMID:16222336</ref>
-[[http://www.uniprot.org/uniprot/IMA2_MOUSE IMA2_MOUSE]] Functions in nuclear protein import as an adapter protein for nuclear receptor KPNB1. Binds specifically and directly to substrates containing either a simple or bipartite NLS motif. Docking of the importin/substrate complex to the nuclear pore complex (NPC) is mediated by KPNB1 through binding to nucleoporin FxFG repeats and the complex is subsequently translocated through the pore by an energy requiring, Ran-dependent mechanism. At the nucleoplasmic side of the NPC, Ran binds to importin-beta and the three components separate and importin-alpha and -beta are re-exported from the nucleus to the cytoplasm where GTP hydrolysis releases Ran from importin. The directionality of nuclear import is thought to be conferred by an asymmetric distribution of the GTP- and GDP-bound forms of Ran between the cytoplasm and nucleus. [[http://www.uniprot.org/uniprot/NUP50_MOUSE NUP50_MOUSE]] Component of the nuclear pore complex that has a direct role in nuclear protein import. Actively displaces NLSs from importin-alpha, and facilitates disassembly of the importin-alpha:beta-cargo complex and importin recycling. Interacts with multiple transport receptor proteins including CDKN1B. This interaction is required for correct intracellular transport and degradation of CDKN1B.<ref>PMID:16222336</ref>
-==About this Structure==
+From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
-[[2c1m]] is a 2 chain structure with sequence from [http://en.wikipedia.org/wiki/Mus_musculus Mus musculus]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=2C1M OCA].
+</div>
+<div class="pdbe-citations 2c1m" style="background-color:#fffaf0;"></div>
 ==See Also==
-*[[Nucleoporin|Nucleoporin]]
+*[[Importin 3D structures|Importin 3D structures]]
+*[[Nucleoporin 3D structures|Nucleoporin 3D structures]]
-==Reference==
+== References ==
-<ref group="xtra">PMID:016222336</ref><references group="xtra"/><references/>
+<references/>
+__TOC__
+</StructureSection>
+[[Category: Large Structures]]
 [[Category: Mus musculus]]
-[[Category: Matsuura, Y.]]
+[[Category: Matsuura Y]]
-[[Category: Stewart, M.]]
+[[Category: Stewart M]]
-[[Category: Importin-alpha]]
-[[Category: Nuclear protein]]
-[[Category: Nuclear transport-complex]]
-[[Category: Nuclear transport-complex nup50]]
-[[Category: Nucleoporin nup50]]
-[[Category: Protein transport]]
-[[Category: Protein transport-membrane protein complex]]
-[[Category: Protein transport/membrane protein]]